Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections.
Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections.
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DOI：
10.1038/jid.2010.123
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发表时间：
2010-09
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影响因子：
--
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由上皮细胞产生的抗微生物肽是抵抗感染性病原体的基本防御。在这项研究中，我们评估了表皮葡萄球菌是否可以增强角质形成细胞产生抗菌肽，从而增强皮肤对感染的防御。将培养的未分化的人角质形成细胞暴露于来自S.表皮葡萄球菌条件培养基（SECM）能增强人β-防御素2（hBD 2）和hBD 3 mRNA的表达，并增强细胞裂解物抑制A组链球菌（GAS）和S.金黄色。hBD 3的部分基因沉默抑制了这种抗菌作用。这种效应在体内是相关的，因为向小鼠施用SECM降低了对GAS感染的易感性。Toll样受体2（TLR 2）对于该过程是重要的，因为TLR 2中和抗体阻断hBD 2和3的诱导，并且TLR 2缺陷小鼠没有显示mBD 4的诱导。总之，这些发现揭示了正常肠道细菌S的潜在用途。表皮细胞活化TLR 2信号传导并诱导抗菌肽表达，从而使皮肤能够对病原体产生增强的反应。
Production of antimicrobial peptides by epithelia is an essential defense against infectious pathogens. In this study we evaluated whether the commensal microorganism Staphylococcus epidermidis may enhance production of antimicrobial peptides by keratinocytes and thus augment skin defense against infection. Exposure of cultured undifferentiated human keratinocytes to a sterile nontoxic small molecule of < 10 kDa from S. epidermidis conditioned culture medium (SECM), but not similar preparations from other bacteria, enhanced human β-defensin 2 (hBD2) and hBD3 mRNA expression and increased the capacity of cell lysates to inhibit the growth of group A Streptococcus (GAS) and S. aureus. Partial gene silencing of hBD3 inhibited this antimicrobial action. This effect was relevant in vivo as administration of SECM to mice decreased susceptibility to infection by GAS. Toll-like receptor 2 (TLR2) was important to this process as a TLR2-neutralizing antibody blocked induction of hBDs 2 and 3, and Tlr2-deficient mice did not show induction of mBD4. Taken together, these findings reveal a potential use for normal commensal bacterium S. epidermidis to activate TLR2 signaling and induce antimicrobial peptide expression, thus enabling the skin to mount an enhanced response to pathogens.
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影响因子：
30.5
作者：
Fukao, T;Tanabe, M;Koyasu, S
通讯作者：
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影响因子：
46.9
作者：
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影响因子：
3.1
作者：
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影响因子：
16.8
作者：
Fukao, T;Koyasu, S
通讯作者：
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DOI：
10.1073/pnas.0807920105
发表时间：
2008-11-18
影响因子：
11.1
作者：
Fierer, Noah;Hamady, Micah;Knight, Rob
通讯作者：
Knight, Rob